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Xuezhu Wang,1,&ast; Xu Yang,2,&ast; Jingnan Wang,1 Chengyan Dong,3 Jie Ding,1 Meiqi Wu,1 Yanyu Wang,2 Haiyan Ding,4 Hui Zhang,4 Xinting Sang,2 Haitao Zhao,2 Li Huo1 1Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3GE Healthcare China, Beijing, People’s Republic of China; 4Department of Biomedical Engineering, Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Huo; Haitao Zhao, &num;1 Shuaifuyuan, Dongcheng District, Beijing, People’s Republic of China, Tel +86 13910801986; +86 13901246374, Email huoli@pumch.cn; zhaoht@pumch.cnPurpose: The combination of PD-1/PD-L1 inhibitors and molecular targeted agents showed promising efficacy for unresectable hepatocellular carcinoma (uHCC). This study aimed to investigate the prognostic value of metabolic parameters from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in patients with uHCC underwent the combined therapies.Patients and Methods: Patients with uHCC treated with a combination of immunotherapy and targeted therapy who underwent baseline 18F-FDG PET/CT between July 2018 and December 2021 were recruited retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake values (SUVmax), and clinical and biological parameters were recorded. A multivariate prediction model was developed for overall survival (OS) using these parameters together with clinical prognostic factors.Results: Seventy-seven patients were finally included. The median OS was 16.8 months. We found that a high MTV (≥ 39.65 cm3 as the median value) was significantly associated with OS (P< 0.05). In multivariate analyses for OS, a high MTV, high Eastern Cooperative Oncology Group performance status (ECOG-PS, ≥ 1), Child-Pugh (B-C) grade, and the presence of bone metastasis were significantly associated with poor OS (HR 1.371, HR 3.73, HR 15.384, and HR 2.994, all P< 0.05, respectively). A multivariate prognostic model including MTV and prognostic factors, such as ECOG-PS, Child-Pugh grade, and bone metastasis, further improved the identification of different OS subgroups.Conclusion: High MTV is an adverse prognostic factor in patients with uHCC treated with a combination of immunotherapy and molecular targeted agents. Integrating PET/CT parameters with clinical prognostic factors could help to personalize immunotherapy.Graphical Abstract: Keywords: unresectable hepatocellular carcinoma, PD-1 inhibitor, PD-L1 inhibitor, PET/CT, metabolic tumor volume, prognostic model

The Atlantic Meridional Overturning Circulation (AMOC), a key component of the climate system, is projected to weaken in the 21st century. Using the Alfred Wegener Institute Climate Model (AWI-CM 1.1 LR), we conduct a set of numerical experiments to investigate the transient response of AMOC to anthropogenic warming with quadrupled carbon dioxide (4×CO2). The results suggest that circulation adjustment outside the Arctic dominates the AMOC weakening. In warming conditions, northward advection transport from the southern flank of the Atlantic subpolar region will increase, which is expected to enhance the upper ocean stratification over deep convection zones and inhibit deep-water formation, thus weakening the AMOC largely. Stratification enhancement is more pronounced in Nordic Seas than that in the Labrador Sea, implying a more direct role of Labrador Sea in evolution of still-active AMOC. In Nordic Seas, decreased ocean convection is dominated by temperature contributions due to a substantial increase of northward advective heat transport. While in Labrador Sea, both surface heat flux and advective heat transport matter, with comparable thermohaline contributions.

Background Sexual health is an essential part of overall well-being, and medical students’ sexual education, level of sexual knowledge, and attitudes toward sexual health will affect their sexual behavior. Aim To explore the correlation among medical decision tendency, sex education level, and sexual health KAP (knowledge, attitudes, and practices). Methods We conducted a cross-sectional survey in March 2019. Data were collected via online surveys with a self-developed questionnaire covering sexual KAP and sexual education. We used Spearman correlation to assess the effect of sexual education on KAP after scoring the related questions. Outcomes Outcomes included descriptive analysis and correlation of medical and nursing students’ KAP and education regarding sexual health. Results Medical and nursing students hold a high level of sexual knowledge (74.8%) and a positive attitude toward premarital sex (87.5%) and homosexuality (94.5%). By conducting the correlation analysis, we observed that medical and nursing students’ tendency to support friends’ homosexuality was positively correlated with the view that medical intervention for transgender or gay/lesbian people is unnecessary (P Clinical Translation Medical and nursing students who want more diverse sexual education and who had higher scores in the sexual knowledge test tend to provide their patients with more humanistic care regarding sexual needs. Strengths and Limitations The research shows the current situation of medical and nursing students’ sexual education experience and preference and sexual knowledge, attitudes, and behavior. Heat maps were used to more intuitively describe the correlation between medical students’ characteristics and their sexual knowledge, attitudes, and behaviors and sex education. The results may not be generalizable across China, as the participants were from 1 medical school. Conclusion It is essential to provide sexual education for medical and nursing students to ensure a more humanistic approach to patient care regarding sexual needs; therefore, we recommend that medical schools invest in sexual education for medical and nursing students throughout their education.

Using the Alfred Wegener Institute Climate Model (AWI-CM 1.1 LR), we conduct sensitivity experiments separating the Arctic and extra-Arctic warming to investigate the transient response of AMOC to quadrupled carbon dioxide (4×CO2) forcings. The results suggest that AMOC weakening is primarily affected by circulation adjustment induced by the outer-Arctic warming, while the effects of Arctic warming are confined to the polar range and contribute less to AMOC changes. When warming forcing is applied outside the Arctic, the increases of northward advective heat transport dominate the weakening of deep convection in the Nordic Seas, while the reduction of heat loss from ocean to atmosphere is prevalent in Labrador Sea. Besides, the weakening of deep convection in Nordic Seas is more pronounced than in Labrador Sea, implying a leading role of Nordic Seas in the weakening of AMOC under global warming.

Background Dynamic PET with kinetic modeling was reported to be potentially helpful in the assessment of hepatic malignancy. In this study, a kinetic modeling analysis was performed on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) from dynamic FDG positron emission tomography/computer tomography (PET/CT) scans. Methods A reversible two-tissue compartment model with dual blood input function, which takes into consideration the blood supply from both hepatic artery and portal vein, was used for accurate kinetic modeling of liver dynamic 18F-FDG PET imaging. The blood input functions were directly measured as the mean values over the VOIs on descending aorta and portal vein respectively. And the contribution of hepatic artery to the blood input function was optimization-derived in the process of model fitting. The kinetic model was evaluated using dynamic PET data acquired on 24 patients with identified hepatobiliary malignancy. 38 HCC or ICC identified lesions and 24 healthy liver regions were analyzed. Results Results showed significant differences in kinetic parameters $${K}_{1}-{k}_{4}$$ K 1 - k 4 , blood supplying fraction $${f}_{A}$$ f A , and metabolic rate constant $${K}_{i}$$ K i between malignant lesions and healthy liver tissue. And significant differences were also observed in $${K}_{1}$$ K 1 , $${k}_{3}$$ k 3 , $${f}_{A}$$ f A and $${K}_{i}$$ K i between HCC and ICC lesions. Further investigations of the effect of SUV measurements on the derived kinetic parameters were conducted. And results showed comparable effectiveness of the kinetic modeling using either SUVmean or SUVmax measurements. Conclusions Dynamic 18F-FDG PET imaging with optimization-derived hepatic artery blood supply fraction dual-blood input function kinetic modeling can effectively distinguish malignant lesions from healthy liver tissue, as well as HCC and ICC lesions.

Light-chain amyloidosis (AL) is characterised by a systematic deposition of amyloidogenic immunoglobulin light chains produced by pathogenic bone marrow plasma cells (BMPCs), the features of which remain elusive. Herein, we conducted a single-cell RNA-seq and image flow cytometry analysis of BMPCs in AL in comparison with those in healthy controls and their precursors: monoclonal gammopathy of undetermined significance (MGUS). We identified seven BMPC subsets with overlapping but distinct functions such as DNA repair, cell proliferation, osteoclast differentiation, chromatin organisation, and immunoglobulin production. The subsets enriched in AL overexpressed amyloid-beta binding protein-encoding genes, such as apolipoprotein E (APOE) and cystatin 3 (CST3), and exhibited plasmablastic morphology. The subsets related to aberrant light-chain production in AL upregulated pathways of neutrophil degranulation and transportation to as well as modifications in the Golgi apparatus, especially that of N-linked protein glycosylation. The predominant subset was most susceptible to glucocorticoid and proteasome inhibitors and highly expressed venetoclax sensitivity-associated genes in t(11;14) AL. We further validated a patient subgroup featuring a larger proportion of the predominant subset and a higher expression of cyclin D1 (CCND1) and venetoclax sensitivity-associated genes. Our findings provide insights into the mechanisms underlying the functional heterogeneity of BMPCs in AL.

The temporal variation of heat budget in the subsurface layer of the eastern Ross Sea shelf (ERSS) is crucial for understanding the stability of ice shelves in the Ross Sea. In this study, six-year simulations from the Southern Ocean State Estimate (SOSE) are employed to analyze the interannual variations of heat budget in the subsurface layer of ERSS and the controlling mechanisms. The results reveal that the annual change in the heat content of the study region is dominated by the horizontal heat advection term, and only in one year the vertical advection and diffusion terms also play an important role. The horizontal advection term is co-affected by the intrusion of warm circumpolar deep water (CDW) onto the shelf across the northern boundary of ERSS, the transport of cold high salinity shelf water (HSSW) from the western Ross Sea shelf (WRSS), and the transport of CDW across the western boundary of ERSS. Contributions from these physical processes to the change of annual heat content vary over the years. The interannual variation of the CDW intrusion is modulated by the strength of eddy activities over the slope, and the interannual variation of heat transports related to HSSW is affected both by the extent of HSSW on the western shelf and coastal circulations that affect the eastward spreading of HSSW.

Global warming since the industrial revolution has led to a series of changes in the atmosphere and ocean. As a key indicator of global ocean circulation, AMOC has shown a weakening in recent decades from both the observed and simulated results. This process which is not only affected by the local variation of the Arctic, but also by the ocean and atmosphere circulation changes in the middle and lower latitudes, might have important implications for future global climate changes. We employ the Alfred Wegener Institute Climate Model (AWI-CM 1.1 LR) and a method of perturbing coupled models to quantify and understand the impact of anthropogenic warming on the slowdown of AMOC. Conducted one control (CTRL) experiment and three sensitivity experiments (60N, 60NS, and GLOB) in which CO2 concentration were abruptly quadrupled either regionally (60N-north of 60°N, 60NS-south of 60°N) or globally (GLOB). The goal of our research is to identify the response of AMOC weakening to the quadrupling of CO2 concentration in different regions and provide future insight into ocean circulation changes in the context of climate warming. Our results show that CO2 forcing outside the Arctic dominates the weakening of AMOC. In a warming climate, the poleward heat transport increased due to the extra-Arctic CO2 forcing, which enhanced the upper ocean average stratification within the mixed-layer depth over Nordic Seas and Labrador Sea and thus weakens the AMOC to a large extent. The warming in upper-layer also lead to the dominant role of temperature contribution to stratification. However, in both the deep convection regions, the mechanism resulting in the strengthening of stratification might be quite different.

SODA (Simple Ocean Data Assimilation) is one of the ocean reanalysis data widely used in oceanographic research. The SODA3 dataset provides multiple ocean reanalysis data sets driven by different atmospheric forcing fields. The differences between their arctic sea ice simulations are assessed and compared with observational data from different sources. We find that in the simulation of arctic sea ice concentration, the differences between SODA3 reanalysis data sets driven by different forcing fields are small, showing a low concentration of thick ice and a high concentration of thin ice. In terms of sea ice extent, different forced field model data can well simulate the decline trend of observed data, but the overall arctic sea ice extent is overestimated, which is related to more simulated sea ice in the sea ice margin. In terms of the simulation of arctic sea ice thickness, the results of different forcing fields show that the simulation of arctic sea ice thickness by SODA data set is relatively thin on the whole, especially in the thick ice region. The results of different models differ greatly in the Beaufort Sea, the Fram Strait, and the Central Arctic Sea. The above differences may be related to the differences between the model-driven field and the actual wind field, which leads to the inaccurate simulation of arctic sea ice transport and ultimately to the different thickness distribution simulation. In addition, differences in heat flux may also lead to differences in arctic sea ice between models and observations. In this paper, the differences between the results of arctic sea ice driven by different SODA3 forcing fields are studied, which provides a reference for the use of SODA3 data in the study of arctic sea ice and guidance for the selection of SODA data in the study of sea ice in different arctic seas.

Warming of the North Atlantic region in climate history often was associated with massive melting of the Greenland Ice Sheet. To identify the meltwater's impacts and isolate these from internal variability and other global warming factors, we run single‐forcing simulations including small ensembles using three complex climate models differing only in their ocean components. In 200‐year‐long preindustrial climate simulations, we identify robust consequences of abruptly increasing Greenland runoff by 0.05 Sv: sea level rise of 44 ± 10 cm, subpolar North Atlantic surface cooling of 0.7°C, and a moderate AMOC decline of 1.1–2.0 Sv. The latter two emerge in under three decades—and reverse on the same timescale after the perturbation ends in year 100. The ocean translates the step‐change perturbation into a multidecadal‐to‐centennial signature in the deep overturning circulation. In all simulations, internal variability creates notable uncertainty in estimating trends, time of emergence, and duration of the response., Plain Language Summary: Enhanced melting of Greenland's glaciers is considered to be a major player in past rapid climate transitions and anticipated to soon impact ocean circulation under current global warming. Global warming triggers complex processes and feedbacks, of which greater amounts of meltwater slowing the large‐scale ocean circulation is only one. To better understand the sensitivity of the real but also the model ocean to just this meltwater, we run idealized experiments with up‐to‐date climate models, which use the same atmosphere and land but different ocean components. We find that sea level rise, cooling of the North Atlantic region, and slowing of the ocean circulation are responses common to all models while regional magnitudes of these responses differ considerably. Once we stop adding freshwater, all three models show that surface temperature and ocean circulation recover as quickly (or slowly) as they changed at the beginning of the experiment. Sea level rise is a lasting impact though., Key Points: Sudden increase in Greenland freshwater release is turned into century scale change by deep ocean dynamics. Upper ocean responses to moderately enhanced freshwater release from Greenland reverse on the same timescale once release ceases. Ocean model formulation affects regional expressions but basin‐scale responses are robust, so is the timing on decadal to centennial scales., Bundesministerium für Bildung und Forschung (BMBF) http://dx.doi.org/10.13039/501100002347

Although KIAA0101 is involved in many diseases, its expression and prognostic value in HCC remain undefined. According to CCLE, KIAA0101 is highly expressed in HCC, with a weak positive correlation between copy number and gene expression. Four studies involving 760 samples in ONCOMINE report elevated KIAA0101 expression in HCC (p=3.11E-22). The KM plotter revealed high KIAA0101 expression to be associated with worse overall survival in HCC (HR=2.09, p=4.1e-05); this prognostic power was stronger for male than female, early-stage than advanced-stage, and Asian than Caucasian patients. RNA sequencing data for 8 pairs of HCC and adjacent tissue samples validated the significantly high KIAA0101 level (p=0.00497). Moreover, functional annotations of 31 KIAA0101-coexpressed genes show enrichment of terms associated with mitosis, cytoskeleton construction, and chromosome segregation. Among 9 genes having STRING-validated protein-protein interactions with KIAA0101, two are involved in virus-related pathways. Alternative splicing analysis indicated higher expression of variant 1 and variant 2 in HCC and no significant differences in exon usage of KIAA0101 between cancer and normal tissues. These findings support that KIAA0101 is a potential prognostic biomarker for HCC and highlight the association between virus infection and the mechanism underlying the process by which KIAA0101 contributes to poor prognosis of patients.

18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) is an efficient method of diagnosing, staging, treatment evaluation, and recurrence monitoring of pediatric diseases. FDG has some limitations, but other PET/CT tracers have shown promising roles in evaluation of pathologies in pediatric patients. FDG is the most commonly used PET tracer but can accumulate in different types of infection and inflammation. In recent years, more non-FDG tracers have shown utility in evaluating pediatric disease. This article reviews currently available literature on the clinical application of non-FDG PET tracers in the application in the pediatric population.

Endothelial progenitor cells (EPCs) play a major role in regulating pulmonary vascular remodeling during pulmonary arterial hypertension (PAH) development. Several preclinical and clinical trials of EPCs transplantation have been performed for the treatment of PAH. However, there is no reliable method to monitor real-time cell trafficking and quantify transplanted EPCs. Here in this paper we isolated EPCs from human peripheral blood, identified their functional integrity, and efficiently labeled the EPCs with 89Zr-oxine and DiO. Labeled EPCs were injected into the tail vein of normal and PAH rats to be tracked in vivo. From the microPET/CT images, we found EPCs were distributed primarily in the lung at 1 h and then migrated to the liver and spleen. We could observe the 3,3′ dioctadecyloxacarbocyanine perchlorate (DiO)-labeled EPCs binding in the pulmonary vasculature by CellVizio confocal. The result of quantitative analysis revealed significantly higher accumulation of EPCs in the lungs of PAH rats than in those of healthy rats. The distribution and higher accumulation of EPCs in the lungs of PAH rats could help to evaluate the safety and provide evidence of effectiveness of EPC therapy., Graphical Abstract, This article describes the trafficking of endothelial progenitor cells in vivo after labeling with a sensitive radioactive probe. With high-resolution microPET/CT images, Yang and colleagues found high accumulation of EPCs in the lungs of pulmonary hypertension rats, which suggested the potential application of EPCs in lung diseases.

Background This study was designed to investigate the prognostic value of the lymphocyte to monocyte ratio (LMR) in patients with gallbladder carcinoma (GBC). Patients and methods We retrospectively enrolled 154 consecutive GBC patients from 2005 to 2017 in this study. The LMR of preoperative blood samples was calculated by dividing the lymphocyte count by the monocyte count. A receiver operating characteristic (ROC) curve was employed to identify the optimal cut-off value of the LMR in the determination of overall survival (OS). The Kaplan-Meier method was utilized to assess OS, and the Log rank test was employed to compare survival differences. Univariate and multivariate Cox regression analyses were conducted to detect independent prognostic indicators. Results The optimal cut-off point for the LMR was 4.76 according to the ROC curve. Patients ≤60 years old with an LMR ≤4.76 experienced significantly worse OS than those with an LMR >4.76 (hazard ratio (HR): 0.399, 95% confidence interval (CI): 0.265-0.602, P 60 years old or among the entire study cohort (both P>0.05). Significantly poorer OS was observed in patients >60 years with an LMR ≤4.21 compared to those with an LMR >4.21 (HR: 1.830, 95% CI: 1.129-2.967, P=0.014). Multivariate Cox regression analysis indicated that both the high and low LMR cut-off values were independent risk factors for OS (HR: 0.272, 95% CI: 0.105-0.704, P=0.007; HR: 0.544, 95% CI: 0.330-0.895, P=0.017). Conclusion The LMR is an independent prognostic indicator for GBC patients, the cut-off value of which is age dependent.

Brown adipose tissue (BAT) is important in monitoring energy homeostasis and cancer cachexia. Different from white adipose tissue, BAT is characterized by the presence of a large number of mitochondria in adipocytes. Translocator protein 18 kDa (TSPO), a critical transporter, is expressed in the outer membrane of mitochondria. We speculated that [18F]DPA714, a specific TSPO tracer, may monitor BAT activity in tumor-bearing mice in vivo. We first analyzed the radioactive uptake of positron emission tomography (PET) tracers in BAT of CT26 xenograft mice with 18F-fluorodeoxyglucose ([18F]FDG) and [18F]DPA714. We also studied the BAT uptake of [18F]DPA714 in CT26, A549 and LLC tumor models. The dynamic distribution of [18F]FDG is quite variable among animals, even in mice of the same tumor model (%ID/g-mean: mean ± SDM, 8.61 ± 8.90, n = 16). Contrarily, [18F]DPA714 produced high-quality and stable BAT imaging in different tumor models and different animals of the same model. Interestingly, %ID/g-mean of [18F]DPA714 in BAT was significantly higher on day 26 than that on day 7 in CT26 xenograft model. Taken together, these results strongly indicate the potential feasibility of [18F]DPA714 PET imaging in investigating BAT and energy metabolism during tumor progression in preclinical and clinical study.

Systemic amyloid light chain (AL) amyloidosis is the most common type of amyloidosis, leading to cardiomyocyte necrosis and interstitial fibrosis. Gallium-68-labeled fibroblast activation protein inhibitor 04 (The aim of this study was to evaluate the feasibility ofThirty consecutive patients (mean age: 59.1 ± 7.7 years; 20 men, 10 women) with biopsy-proven AL amyloidosis were enrolled prospectively (including 27 with AL CA and 3 without AL CA). All patients underwentOf all patients, 80% (24 of 30) showed increased LV uptake (PET-patchy [n = 4] vs PET-extensive [n = 20]), whereas 6 patients did not show visible myocardial uptake. Standardized uptake value ratio and LV molecular volume were significantly higher in the PET-extensive than the PET-patchy group (2.79 mL ± 1.22 mL vs 1.53 mL ± 0.66 mL [P = 0.045] and 198.3 mL ± 59.97 mL vs 127.8 mL ± 25.82 [P = 0.005], respectively). Additionally

(68)Ga-DOTA-JR11 is a somatostatin receptor subtype 2–specific antagonist used for PET/CT imaging. The purpose of this study was to compare (68)Ga-DOTA-JR11 and (68)Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: Patients with histologically proven, metastatic or unresectable, well-differentiated neuroendocrine tumors were prospectively recruited to this study. Each patient received an intravenous injection of (68)Ga-DOTATATE (155 ± 52 MBq) on the first day and (68)Ga-DOTA-JR11 (148 ± 52 MBq) on the second day. Whole-body PET/CT scans were performed at 40–60 min after injection on the same scanner. Physiologic normal-organ uptake, lesion numbers, and lesion uptake were compared. Results: Thirty-one patients were prospectively enrolled in the study. The SUV(max) of the spleen, renal cortex, adrenal glands, pituitary glands, stomach wall, normal liver parenchyma, small intestine, pancreas, and bone marrow was significantly lower on (68)Ga-DOTA-JR11 than on (68)Ga-DOTATATE PET/CT (P < 0.001). (68)Ga-DOTA-JR11 detected significantly more liver lesions (552 vs. 365, P = 0.001) but fewer bone lesions (158 vs. 388, P = 0.016) than (68)Ga-DOTATATE. The target-to-background ratio of liver lesions was significantly higher on (68)Ga-DOTA-JR11 (7.7 ± 5.4 vs. 3.4 ± 2.0, P < 0.001). (68)Ga-DOTA-JR11 and (68)Ga-DOTATATE PET/CT showed comparable results for primary tumors and lymph node metastases on both patient-based and lesion-based comparisons. Conclusion: (68)Ga-DOTA-JR11 performs better in detecting liver metastases, with a better tumor-to-background ratio, whereas (68)Ga-DOTATATE may outperform (68)Ga-DOTA-JR11 in the detection of bone metastases. However, the lower somatostatin receptor subtype 2 affinity of (68)Ga-DOTA-JR11 than of (177)Lu-DOTA-JR11 may limit its role as a diagnostic pair for the theranostic approach with (177)Lu-DOTA-JR11.

Background: A growing body of evidence has shown that circular RNAs (circRNAs) are promising exosomal cancer biomarker candidates. However, global alterations of circRNAs in cancer and the driving force of circRNA biogenesis remain under investigation. Studies on these factors are needed to identify ideal circRNA biomarkers for cancer.Methods: We comparatively analyzed the circRNA landscape in pan-cancer and normal tissues to investigate their biologically significant characteristics and identify circRNAs enriched in pan-cancer. We used co-expression analysis, LASSO regularization, and support vector machine to analyze 265 pan-cancer and 319 normal tissues to identify circRNAs with the highest ability to distinguish cancer tissues from normal tissues which showed high expression in plasma exosomes from patients with cancer (e.g., hepatocellular carcinoma, HCC) and were associated with cancer mutations. Results: Expression of circRNAs was reduced in cancer tissues and plasma exosomes from patients with cancer than in normal tissues and exosomes from healthy controls. The circRNAs with the strongest ability to distinguish between cancer and normal tissues were among the top 10% of stably expressed circRNAs. Compared with normal-tissue-enriched circRNAs, cancer-tissue‒enriched circRNAs exhibited a more prominent association with cancer mutations and higher levels in plasma exosomes from patients with HCC. Particularly, we identified dynein axonemal heavy chain 14 (DNAH14), which serves as the host gene of three cancer tissue-enriched circRNAs, as one of the top back-spliced genes exclusive to cancer tissues. Among these three circRNAs, chr1_224952669_224968874_+ was significantly elevated in plasma exosomes from patients with HCC and was associated with the cancer mutation chr1:224952669: G>A, a splice acceptor variant that is potentially a driving force of circRNA biogenesis.Conclusions: Our bioinformatic analyses provide insights into the characteristics of the circRNA landscape in cancer and the potential of cancer mutation-associated and cancer tissue-enriched RNAs as plasma exosomal cancer biomarkers. Moreover, our results highlight DNAH14 as a host gene that should be further examined in studies of circRNA in cancer.

We report the imaging findings of 2 cases of cardiac amyloidosis, one light chain (AL) type and another transthyretin (ATTR) type. The images showed 11C-Pittsburgh compound B (11C-PIB) uptake in the heart with AL amyloidosis, whereas the ATTR amyloidosis showed 11C-PIB-negative and 99mTc-PYP-positive uptake in the heart. It demonstrated that using 99mTc-PYP scintigraphy and 11C-PIB PET/CT might be able to differentiate these 2 major types of cardiac amyloidosis noninvasively.

Genetic, epigenetic, and metabolic alterations are all hallmarks of cancer. However, the epigenome and metabolome are both highly complex and dynamic biological networks in vivo. The interplay between the epigenome and metabolome contributes to a biological system that is responsive to the tumor microenvironment and possesses a wealth of unknown biomarkers and targets of cancer therapy. From this perspective, we first review the state of high-throughput biological data acquisition (i.e. multiomics data) and analysis (i.e. computational tools) and then propose a conceptual in silico metabolic and epigenetic regulatory network (MER-Net) that is based on these current high-throughput methods. The conceptual MER-Net is aimed at linking metabolomic and epigenomic networks through observation of biological processes, omics data acquisition, analysis of network information, and integration with validated database knowledge. Thus, MER-Net could be used to reveal new potential biomarkers and therapeutic targets using deep learning models to integrate and analyze large multiomics networks. We propose that MER-Net can serve as a tool to guide integrated metabolomics and epigenomics research or can be modified to answer other complex biological and clinical questions using multiomics data.

Background Dynamic PET with kinetic modeling was reported to be potentially helpful in the assessment of hepatic malignancy. In this study, a kinetic modeling analysis was performed on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) from dynamic FDG positron emission tomography/computer tomography (PET/CT) scans. Methods A reversible two-tissue compartment model with dual blood input function, which takes into consideration the blood supply from both hepatic artery and portal vein, was used for accurate kinetic modeling of liver dynamic 18F-FDG PET imaging. The blood input functions were directly measured as the mean values over the VOIs on descending aorta and portal vein respectively. And the contribution of hepatic artery to the blood input function was optimization-derived in the process of model fitting. The kinetic model was evaluated using dynamic PET data acquired on 24 patients with identified hepatobiliary malignancy. 38 HCC or ICC identified lesions and 24 healthy liver regions were analyzed. Results Results showed significant differences in kinetic parameters \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${K}_{1}-{k}_{4}$$\end{document}K1-k4, blood supplying fraction \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${f}_{A}$$\end{document}fA, and metabolic rate constant \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${K}_{i}$$\end{document}Ki between malignant lesions and healthy liver tissue. And significant differences were also observed in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${K}_{1}$$\end{document}K1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${k}_{3}$$\end{document}k3, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${f}_{A}$$\end{document}fA and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${K}_{i}$$\end{document}Ki between HCC and ICC lesions. Further investigations of the effect of SUV measurements on the derived kinetic parameters were conducted. And results showed comparable effectiveness of the kinetic modeling using either SUVmean or SUVmax measurements. Conclusions Dynamic 18F-FDG PET imaging with optimization-derived hepatic artery blood supply fraction dual-blood input function kinetic modeling can effectively distinguish malignant lesions from healthy liver tissue, as well as HCC and ICC lesions.

A 51-year-old woman with a history of sarcomatoid hepatocellular carcinoma, status post resection, underwent FDG PET/CT. In addition to abnormal activity elsewhere, the images showed focal activity in the isthmus of the thyroid, suggestive of malignant involvement, and diffuse mild activity in the left lobe of the thyroid, suggestive of thyroiditis. After a 10-week anti-PD-1 pembrolizumab therapy, the follow-up FDG PET/CT scan demonstrated much more intense activity in both the isthmus and the left lobe of the thyroid. Pathological examination revealed papillary thyroid cancer in the isthmus and thyroiditis in the left lobe of the thyroid.